The human nervous system comprises highly diverse neuronal cell types that make specific interconnections with one another. Once destroyed, neuronal cells are not regenerative. Thus, there is a long felt need in the biomedical field to be able to generate neurons for use in the treatment of various neurological disorders via either the direct transfer of neuronal cells in a cell therapy approach, or by delivery of potential genetically based drugs, such as nerve growth factors, in a gene therapy approach.
For example, in the case of neurotrauma, stroke and neurodegenerative diseases, such as Parkinson disease, Huntington disease, and Alzheimer disease, the most comprehensive approach to regain neural function is via direct cell therapy to replace the damaged cells with healthy cells. In this cell therapy application, newly generated neurons would be utilized by direct transfer, via grafting and/or transplantation, to a patient in need.
A gene therapy approach, on the other hand, is needed to treat other types of nervous system disorders. Because the brain is protected by a blood-brain barrier that effectively blocks the flow of large molecules into the brain, peripheral injection of potential growth factor drugs, or other potentially therapeutic gene products, is ineffective. Thus, a major challenge facing the biotechnology industry is to find an efficient mechanism for delivering potential gene therapy products, directly to the brain, so as to treat neurological disorders on the molecular level. In this regard, a renewable source of human neural cells could serve as a vehicle to deliver potential gene therapy products to the brain and nervous system.
A major problem, however, for the further progression of neuronal transplantation for the purpose of either cell therapy or gene therapy is the source of donor material. To date, numerous therapeutic transplantations have been performed exploiting various types of human fetal tissue as the source of donor material. Significant ethical and technical issues arise, however, with the use of human fetal tissue as donor material. Examples of technical problems associated with the use of fetal tissue are immunological rejection of the donor material by the host and risk of transmitting disease to the host by the transplanted neuronal cells.
Thus, there is a need in the field of neurological research and applied neurobiology for a renewable source of neurons for use in both cell therapy and gene therapy. Importantly, the use of such cells could eliminate a need for fetal human tissue in therapeutic approaches aimed at restoring neurological function by intracerebral transplantation of nervous system cells.